Pro00031192 - ALD-451

Clinical Trials for Adults | A Pilot Study of the Administration of Bone Marrow Derived Stem Cells (ALD-451) in WHO Grade IV Malignant Glioma

Primary Objective:

  • to demonstrate the safety of intravenously administered autologous bone marrow derived ALD-451 cells following surgery, radiation therapy and temozolomide in patients with WHO grade IV malignant glioma

Secondary Objectives:

  • to determine the recovery of ALD-451 from bone marrow of patients following radiation therapy and chemotherapy
  • to determine if intravenous administration of autologous ALD-451 cells following surgery, radiation therapy and temozolomide in WHO grade IV malignant glioma patients may lessen on subsequent deterioration of neurocognition and patient-reported outcomes.

Study Drug:
ALD-451 is a subpopulation of bone marrow cells that is composed of cells that express high levels of the intracellular enzyme aldehyde dehydrogenase (ALDH).  These cells are referred to as ALDH bright (ALDHbr) cells.  The hypothesis underlying this trial is that ALD-451 cells generated from autologous bone marrow will rescue normal cells and reduce the late effects of radiation therapy. 

Eligibility: Key Criteria:

  • Adults with grade 4 newly diagnosed supratentorial malignant glioma
  • Must have had a gross total resection (less than 1cm of residual disease)
  • Must be able to receive radiation at Duke University Medical Center
  • KPS > 60%
  • Must meet eligibility lab parameters
  • Must be able to interrupt anti-coagulation for bone marrow harvest and dosing procedures.
  • No prior active malignancy requiring treatment within the past 5 years.
  • No prior myocardial infarction within 3 months of study. 
  • Must be able to undergo neurocognitive testing and prescribed patient outcome reporting.
  • Must have blood pressure < 150/95mmHg.

Study Design: Key Features

  • Patients will have gross total resection of primary WHO grade IV malignant glioma.
  • After enrolling into study, patient to undergo 6.5 weeks of radiation with daily Temozolomide at 75mg/m2.
  • Approximately 2 weeks post-radiation, patient will undergo bone marrow harvest where 120mL of bone marrow will be collected from the iliac crest.
  • Two to four days later, patient will be reinfused with ALD-451 cells via peripheral IV over 10-15 minutes.
  • Two weeks later, patient will start Temodar at 150mg/m2 for 5 days.  Second cycle will be dose escalated to 200mg/m2
  • Patients to take a total of 12 cycles of Temodar as long as they remain progression free.

Logistics:

  • Patients will have a MRI and return clinic appt at screening, 2 weeks post XRT/Temo, at the end of cycles 1 and 2 and then every 8 weeks thereafter.
  • During XRT/Temo – CBC w/diff weekly, CMP to be collected monthly.
  • During 5 day Temo – CBC w/diff to be collected on days 21 and 28 of each cycle, CMP to be collectedon day 28 of each cycle.
  • Neurocognitive testing to take place at baseline, 2 weeks post XRT/Temo and after cycles 6 and 12 of Temodar.

Re-treatment criteria

  •  Initiation of each cycle will require:
    • ANC > 1,000cells,ul
    • Platelets > 100,000/ul
    • Creatinine < 1.8
    • AST < 2x ULN
    • T bili < 2 x ULN






This article comes from The Preston Robert Tisch Brain Tumor Center at Duke   http://www.cancer.duke.edu/btc
The URL for this story is:   http://www.cancer.duke.edu/btc/modules/ClinicalTrials4/index.php?id=112